Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas

Abstract

IntroductionPancreatic and periampullary adenocarcinomas are associated with abnormal body composition visible on CT scans, including low muscle mass (sarcopenia) and low muscle radiodensity due to fat infiltration in muscle (myosteatosis). The biological and clinical correlates to these features are poorly understood.MethodsClinical characteristics and outcomes were studied in 123 patients who underwent pancreaticoduodenectomy for pancreatic or non-pancreatic periampullary adenocarcinoma and who had available preoperative CT scans. In a subgroup of patients with pancreatic cancer (n = 29), rectus abdominus muscle mRNA expression was determined by cDNA microarray and in another subgroup (n = 29) 1H-NMR spectroscopy and gas chromatography-mass spectrometry were used to characterize the serum metabolome.ResultsMuscle mass and radiodensity were not significantly correlated. Distinct groups were identified: sarcopenia (40.7%), myosteatosis (25.2%), both (11.4%). Fat distribution differed in these groups; sarcopenia associated with lower subcutaneous adipose tissue (P<0.0001) and myosteatosis associated with greater visceral adipose tissue (P<0.0001). Sarcopenia, myosteatosis and their combined presence associated with shorter survival, Log Rank P = 0.005, P = 0.06, and P = 0.002, respectively. In muscle, transcriptomic analysis suggested increased inflammation and decreased growth in sarcopenia and disrupted oxidative phosphorylation and lipid accumulation in myosteatosis. In the circulating metabolome, metabolites consistent with muscle catabolism associated with sarcopenia. Metabolites consistent with disordered carbohydrate metabolism were identified in both sarcopenia and myosteatosis.DiscussionMuscle phenotypes differ clinically and biologically. Because these muscle phenotypes are linked to poor survival, it will be imperative to delineate their pathophysiologic mechanisms, including whether they are driven by variable tumor biology or host response.

Myosteatosis is associated with poor physical fitness in patients undergoing hepatopancreatobiliary surgery

“…While reduced length of stay, post‐operative morbidity, and critical care dependency have been observed in cardiothoracic patients undergoing prehabilitation programmes, there are limited data examining its subsequent impact on post‐operative outcomes following abdominal surgery . Moreover, understanding the underlying molecular mechanisms of muscle loss and interrogating distinct muscle phenotypes and their relationship to cancer surgery morbidity and survival are urgently needed. This is key to inform the development of interventions and treatment strategies to mitigate against poor outcomes …”

Computed Tomography-Assessed Sarcopenia Indexes Predict Major Complications following Surgery for Hepatopancreatobiliary Malignancy: A Meta-Analysis

“…As shown in Figure 2a, based on 18 studies [11, 13, 19, 21, 23-28, 32, 34, 36-39, 40, 42] comprising 3,501 patients and 782 major complications, low preoperative SMI was associated with an increased risk of major complications (RR 1.36; 95% CI 1.14-1.63; p = 0.0008; I 2 = 24%). MA and RA As shown in Figure 2c, based on 5 studies [13,24,37,38,41] comprising 885 patients and 221 major complications, preoperative incidence of sarcopenia, which was defined by MA/radiation attenuation on CT was associated with an increased risk of major complications (RR 1.40; 95% CI 1.14-1.73; p = 0.002; I 2 = 4%).…”

“…Fifteen studies [11,13,[20][21][22][23] [32], and 1 in China [26]. Among the included studies, 13 studies were directed at liver [11,13,[19][20][21][22][23][24][25][26][27][28][29] malignancy, 2 bile duct [30,31], 6 pancreas [12,14,[32][33][34][35], 2 periampullary [36,37], 4 periampullary and pancreas [38][39][40][41], and 1 hepatopancreatobiliary [42]. The sample size ranged from 67 to 763.…”

“…All of the image analysis was based on CT, and the third lumbar vertebra was the most commonly used level. SMI/ TAMA was the most commonly used index, and it was used in 16 studies [11, 13, 19, 21, 23-28, 32, 34, 36-39], with SBI in 2 studies [40,42], PMI/TPA in 7 studies [12,20,22,[29][30][31]33], MA/RA in 5 studies [13,24,37,38,41], IMAC in 4 studies [20,27,31,33], HUAC in 1 study [35], LPMA in 1 study [14], and TPV in 1 study [12] ( Table 3).…”

Myosteatosis to predict inferior perioperative outcome in patients undergoing orthotopic liver transplantation

“…It varies among individuals as a result of differences in age, body density, and the degree of obesity. [5][6][7] In the face of critical organ shortage with increased utilization of marginal allografts procured from extended criteria donors (ECD), one of the most challenging clinical decisions in the liver transplantation setting is the optimal risk-quantification and the identification of high-risk recipients and/or donor-recipient combinations. 2,3 Besides the pure loss of muscle mass and function known as sarcopenia, qualitative structural changes, such as myosteatosis, characterized by the presence of inter-and intramyocellular fat deposition, 4 have been shown to be associated with reduced muscle strength and poor clinical outcomes in patients undergoing surgery for colorectal or pancreatic cancer.…”